Roles of G protein and beta-arrestin in dopamine D2 receptor-mediated ERK activation.
ERK activation by dopamine D(2) receptor (D(2)R) has been extensively characterized in various cell types including brain tissues. However, the involvement of beta-arrestin in the D(2)R-mediated ERK activation is not clear yet. Three different strategies were employed in this study to determine the roles of G protein or beta-arrestin in D(2)R-mediated ERK activation. The cellular level of beta-arrestins was reduced by RNA interference and pertussis toxin-insensitive Gi proteins were used to identify the G protein involved. Finally point mutations of D(2)R in which coupling with G protein was abolished but the interaction with beta-arrestin was increased, were employed to determine whether the affinity between D(2)R and beta-arrestin is a critical factor for beta-arrestin-mediated ERK activation. Our results show that G(i2) protein is involved in D(2)R-mediated ERK activation but beta-arrestins are either not involved or play minor role.
Quan
Wenying
W
Department of Pharmacology, College of Pharmacy, Chonnam National University, Kwang-Ju 500-757, Republic of Korea.
Kim
Ju-Heon
JH
Department of Pharmacology, College of Pharmacy, Chonnam National University, Kwang-Ju 500-757, Republic of Korea.
Albert
Paul R
PR
Ottawa Health Research Institute, University of Ottawa, 451 Smyth Road, Ottawa, Canada K1H-8M5.
Choi
HyunJin
H
Department of Pharmacology, College of Pharmacy, Chonnam National University, Kwang-Ju 500-757, Republic of Korea.
Kim
Kyeong-Man
KM
Department of Pharmacology, College of Pharmacy, Chonnam National University, Kwang-Ju 500-757, Republic of Korea. Electronic address: kmkim@jnu.ac.kr.
D019390:Arrestins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D037342:Pertussis Toxin / Q000494:pharmacology; D034622:RNA Interference; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D000071557:beta-Arrestins
D019390:Arrestins; D017448:Receptors, Dopamine D2; D000071557:beta-Arrestins; D037342:Pertussis Toxin; D048049:Extracellular Signal-Regulated MAP Kinases; D051960:GTP-Binding Protein alpha Subunit, Gi2